Estimates the proportion of subjects with homozygous sickle cell disease who have a benign clinical course, and assesses factors that may be predictive of benign disease. The subjects (n = 280) were participants in a longitudinal cohort study of sickle cell disease. They were classified as benign or control based on clinical history from birth to age 13 years old. Associations with growth, hematology, and an index of social status were investigated. Benign disease occurred in 43 (15 percent) patients. Neither growth nor social status were related to benign disease. There were only two statistically independent association: alpha thalassemia status and average steady state fetal hemoglobin (HbF). Patients with a normal complement of alpha globin genes were 2.2 (1.0, 4.9) times more likely to have frequent painful crises, dactylitis, and bone necrosis. The odds of having benign disease were 1.09 (1.02, 1.17) times higher for each unit increase in HbF, and 44 percent of subjects with HbF in the top decile (HbF 13.8 percent) of the distribution had benign disease. There was no evidence for a threshold effect of high HbF on benign disease. Concluded that benign clinical course of sickle cell disease may occur in Jamaica and is associated with a normal alpha globin gene complement, and high levels of HbF. Ability to predict benign disease at birth is limited.....read more